This study aims to elucidate the regulatory mechanisms governing the activation of hepatic stellate cells (HSCs), the key effector cells in liver fibrosis, which represents an early pathological stage of metabolic dysfunction–associated steatohepatitis (MASH), and to propose antifibrotic therapeutic strategies based on these mechanisms. Using an integrated multi-omics approach that combines untargeted metabolomics, lipidomics, and transcriptomics, we systematically characterize intracellular metabolic alterations associated with HSC activation and deactivation processes and identify key fibrosis-related molecular factors. Furthermore, pathway- and network-based analyses of integrated omics data are performed to propose novel therapeutic target candidates for the suppression of liver fibrosis and the treatment of MASH.